Improved Postprandial Glycemic Control With Biphasic Insulin Aspart Relative to Biphasic Insulin Lispro and Biphasic Human Insulin in Patients With Type 2 Diabetes

Abstract

OBJECTIVE—The rapid-acting insulin analogs aspart and lispro have now been developed in biphasic formulations. This trial compared the postprandial serum glucose control of biphasic insulin aspart 30 (BIAsp 30: 30% aspart, 70% protaminated aspart) with that of biphasic insulin lispro 25 (Mix25: 25% lispro, 75% protaminated lispro) and biphasic human insulin 30 (BHI 30: 30% regular insulin, 70% NPH insulin) in insulin-treated subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS—This was an open-labeled, randomized, single-dose, three-way crossover trial of 61 insulin-treated subjects with type 2 diabetes who had no significant late diabetic complications. BIAsp 30 and Mix25 were injected subcutaneously immediately before a test meal, and BHI 30 was injected 15 min before a test meal. The primary target of analysis was serum glucose excursion 0–5 h after a meal. RESULTS—The postprandial glycemic control with BIAsp 30, as assessed by the 5-h postmeal serum glucose excursion, was superior to that with both BHI 30 and Mix25 (16.6 ± 4.5 vs. 20.1 ± 4.9 and 18.9 ± 6.1 mmol/l per hour, respectively; P < 0.001 and P < 0.05). For BIAsp 30 versus BHI 30, this was supported by a reduced maximum glucose concentration [Cmax(SG)] (−5%; P < 0.05) occurring earlier (−13 min; P < 0.01). Furthermore, BIAsp 30 displayed a higher maximum serum insulin concentration (+101%; P < 0.001) occurring earlier (−55 min; P < 0.001) compared with BHI 30. Compared with Mix25, there was a shorter time to Cmax(SG) (−11 min; P < 0.05) after treatment with BIAsp 30. CONCLUSIONS—This trial demonstrates that BIAsp 30 improves postprandial glycemic control compared with both Mix25 and BHI 30 in subjects with type 2 diabetes.

Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin aspart and insulin glargine in people with type 2 diabetes

“…Postprandial hyperglycaemia is acknowledged as an inde- pendent risk factor for macrovascular disease and mortality [13,14]. The results from the present study suggest that postprandial glucose excursions in people with type 2 diabetes would be more effectively controlled with BIAsp 30 than with the basal insulin IGlarg when given as monotherapy unsupported by OHAs with secretagogue properties [9]. In clinical practice, however, IGlarg is normally added to OHAs when these preparations, either as monotherapy or combination therapy, have failed to achieve the desired glycaemic targets.…”

“…Plasma insulin rose rapidly after each injection of BIAsp 30, reaching a peak within 2-3 h after injection. In this way, BIAsp 30 approached the desired serum insulin profile for the purpose of controlling postprandial glucose [9]. However following the rapid increase in plasma insulin there was a slow decline towards baseline because of the intermediate-acting, protaminated IAsp component.…”

AHRQ's Comparative Effectiveness Research on Premixed Insulin Analogues for Adults with Type 2 Diabetes: Understanding and Applying the Systematic Review Findings

“…• Insulin aspart 70/30 versus insulin lispro 75/25-2 randomized crossover studies 37,59 • Insulin lispro 75/25 versus insulin lispro 50/50-1 randomized crossover study 41 • Insulin lispro 75/25 versus morning insulin lispro 50/50 plus dinner insulin lispro 75/25-1 randomized crossover study 60 No treatment-group differences were observed for changes in fasting blood glucose. However, 2 studies indicated that postprandial glucose concentration was reduced to a greater extent in patients treated with insulin lispro 50/50 than with insulin lispro 75/25 (P < 0.05 and P = 0.001, respectively).…”

“…• Insulin aspart 70/30 versus NPH/regular 70/30-3 parallel-arm trials 31,33,34 and 3 crossover trials [35][36][37] • Insulin lispro 75/25 versus NPH/regular 70/30 or NPH/regular 50/50-9 randomized crossover studies [37][38][39][40][41][42][43][44][45] and 1 retrospective observational study 28 • Insulin lispro 50/50 versus NPH/regular 70/30 or NPH/ regular 50/50-3 randomized crossover studies 38,41,46 and 1 parallel-arm study 47 The studies varied considerably in therapy administration methods, dosing schedules, and duration.…”

Response to comment on: Nauck MA, Duran S, Kim D et al (2007) A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50:259–267

“…At the time, we chose biphasic insulin aspart 30 as the comparator insulin because a pharmacodynamic assessment following a test meal indicated lower serum glucose excursions with biphasic insulin aspart 30 compared with biphasic human insulin 30 and Mix25 [8]. Since improved postprandial glucose is an important glucoregulatory attribute of exenatide, we did not want to disadvantage the insulin arm in any way.…”